Salicylate‐induced translocation of prestin having mutation in the GTSRH sequence to the plasma membrane

Kumano, Shun; Iida, Kei; Ishihara, Kenji; Murakoshi, Michio; Tsumoto, Kouhei; Ikeda, Katsuhisa; Kumagai, Izumi; Kobayashi, Toshimitsu; Wada, Hiroshi

doi:10.1016/j.febslet.2010.04.010

Cited by 6 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collectively, these observations suggest that the R130S mutation impairs membrane targeting, consistent with previous studies suggesting the importance of the R130 region within the prestin molecule for targeting [13, 35]. …”

Section: Resultssupporting

confidence: 90%

The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein

et al. 2016

View full text Add to dashboard Cite

A missense mutation, R130S, was recently found in the prestin gene, SLC26A5, of patients with moderate to severe hearing loss (DFNB61). In order to define the pathology of hearing loss associated with this missense mutation, a recombinant prestin construct harboring the R130S mutation (R130S-prestin) was generated, and its functional consequences examined in a heterologous expression system. We found that R130S-prestin targets the plasma membrane but less efficiently compared to wild-type. The voltage operating point and voltage sensitivity of the motor function of R130S-prestin were similar to wild-type prestin. However, the motor activity of R130S-prestin is greatly reduced at higher voltage stimulus frequencies, indicating a reduction in motor kinetics. Our study thus provides experimental evidence that supports a causal relationship between the R130S mutation in the prestin gene and hearing loss found in patients with this missense mutation.

show abstract

Section: Resultssupporting

confidence: 90%

The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The nonlinear capacitance change involved in prestin requires some ions such as Cl À and HCO3 À and is inhibited by 10 mM of salicylate (Oliver et al, 2001). Recently, we have reported that salicylate induces the translocation of prestin mutants to the plasma membrane from the cytoplasm (Kumano et al, 2010). There is approximately a 45% similarity between pendrin and prestin in amino acid sequences and transport of anions by pendrin is similar to those transported by prestin (Mount and Romero, 2004).…”

Section: Discussionmentioning

confidence: 95%

“…Recently, we have reported that salicylate, which binds to prestin with high affinity (Tunstall et al, 1995;Kakehata and Santos-Sacchi, 1996), induces the translocation of prestin mutants to the plasma membrane from the cytoplasm (Kumano et al, 2010). Prestin is a member of the SLC26A gene family including pendrin, and there is approximately a 45% similarity between these proteins in amino acid sequences.…”

Section: Introductionmentioning

confidence: 98%

Salicylate restores transport function and anion exchanger activity of missense pendrin mutations

Ishihara¹,

Okuyama²,

Kumano³

et al. 2010

Hearing Research

Self Cite

View full text Add to dashboard Cite

“…For NLC measurements, cells were examined 24 -48 h after transfection. In one experimental series (C415S), 10 M salicylate was added to the medium to promote translocation to the plasma membrane (Kumano et al 2010). Salicylate blocks prestin NLC, so the salicylate was removed at least 1 h before electrophysiological measures (Kakehata and Santos-Sacchi 1996;Tunstall et al 1995).…”

Section: Methodsmentioning

confidence: 99%

The roles of conserved and nonconserved cysteinyl residues in the oligomerization and function of mammalian prestin

Currall

Rossino

Jensen-Smith

et al. 2011

Journal of Neurophysiology

View full text Add to dashboard Cite

The creation of several prestin knockout and knockin mouse lines has demonstrated the importance of the intrinsic outer hair cell membrane protein prestin to mammalian hearing. However, the structure of prestin remains largely unknown, with even its major features in dispute. Several studies have suggested that prestin forms homo-oligomers that may be stabilized by disulfide bonds. Our phylogenetic analysis of prestin sequences across chordate classes suggested that the cysteinyl residues could be divided into three groups, depending on the extent of their conservation between prestin orthologs and paralogs or homologs. An alanine scan functional analysis was performed of all nine cysteinyl positions in mammalian prestin. Prestin function was assayed by measurement of prestin-associated nonlinear capacitance. Of the nine cysteine-alanine substitution mutations, all were properly membrane targeted and all demonstrated nonlinear capacitance. Four mutations (C124A, C192A, C260A, and C415A), all in nonconserved cysteinyl residues, significantly differed in their nonlinear capacitance properties compared with wild-type prestin. In the two most severely disrupted mutations, substitution of the polar residue seryl for cysteinyl restored normal function in one (C415S) but not the other (C124S). We assessed the relationship of prestin oligomerization to cysteine position using fluorescence resonance energy transfer. With one exception, cysteine-alanine substitutions did not significantly alter prestin-prestin interactions. The exception was C415A, one of the two nonconserved cysteinyl residues whose mutation to alanine caused the most disruption in function. We suggest that no disulfide bond is essential for prestin function. However, C415 likely participates by hydrogen bonding in both nonlinear capacitance and oligomerization.

show abstract

Salicylate‐induced translocation of prestin having mutation in the GTSRH sequence to the plasma membrane

Cited by 6 publications

References 16 publications

The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein

The R130S mutation significantly affects the function of prestin, the outer hair cell motor protein

Salicylate restores transport function and anion exchanger activity of missense pendrin mutations

The roles of conserved and nonconserved cysteinyl residues in the oligomerization and function of mammalian prestin

Contact Info

Product

Resources

About